title: Venoconstriction by angiotensin II in the human forearm is inhibited by losartan but not by nicardipine.
abstract: Arterial constriction by angiotensin II (Ang II) in the human forearm is inhibited by the infusion of the AT1-receptor antagonist losartan. We investigated venous constriction by Ang II in the forearm of 19 healthy subjects (23 +/- 1 years) and the inhibitory effects of losartan. Furthermore, we investigated, in both the arterial and venous systems, whether the constrictor effects of Ang II are calcium influx dependent by determining the influence of nicardipine. Arterial forearm blood flow (FBF) and maximal venous outflow (MVO) were measured by venous-occlusion plethysmography. Sodium nitroprusside (5-12.5 ng/kg/min) was infused to predilate the forearm vasculature. Ang II (0.1, 1, and 10 ng/kg/min) was infused before and during losartan (0.3 and 3 microg/kg/min) or nicardipine (0.05 and 0.15 microg/kg/min), respectively. Ang II decreased FBF (Emax-FBF) by 79 +/- 4% and MVO (Emax-MVO) by 28 +/- 3% (p < 0.05). Nicardipine at 0.05 and 0.15 microg/kg/min reduced Emax-FBF from -79 +/- 4% to -48 +/- 4% and -6 +/- 2%, respectively (p < 0.05). Losartan in both doses completely inhibited Emax-MVO (p < 0.05), whereas nicardipine did not influence the venoconstriction by Ang II (p > 0.05). In conclusion, Ang II causes a constriction of both arteries and veins in the human forearm, which may be inhibited by losartan. The arterial constriction appears to be caused by an AT1-receptor-mediated calcium influx via L-type calcium channels. In contrast, the venoconstrictor effect of Ang II proved insensitive to the calcium antagonist nicardipine.
authors.affiliation: Department of Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Baan
authors.forename: P C
authors.initials: PC
authors.lastname: Chang
authors.forename: P
authors.initials: P
authors.lastname: Vermeij
authors.forename: M
authors.initials: M
authors.lastname: Pfaffendorf
authors.forename: P A
authors.initials: PA
authors.lastname: van Zwieten
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000502:physiology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects; D005542:Forearm / Q000098:blood supply* / Q000502:physiology; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D000804:Angiotensin II; D009529:Nicardipine; D019808:Losartan